Intrathecal administration of the adenosine A1 receptor agonist R-phenylisopropyl adenosine reduces presumed pain behaviour in a rat model of central pain

Sjölund, Karl-Fredrik; Heijne, Margareta von; Hao, Jing‐Xia; Xu, Xiao‐Jun; Sollevi, Alf; Wiesenfeld‐Hallin, Zsuzsanna

doi:10.1016/s0304-3940(98)00092-5

Cited by 43 publications

(17 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Together, this indicates that EC is a noxious cold stimulus. EC has been used previously in behavioral studies, and similar temperature changes have been reported (Hao et al, 1996(Hao et al, , 1999Sjolund et al, 1998). These temperature changes are sufficiently cold to activate populations of nociceptive afferents (LaMotte and Thalhammer, 1982;Lynn and Carpenter, 1982;Leem et al, 1993;Kajander, 1996, 1997).…”

Section: Neural Mechanisms Of Cold Somatosensationmentioning

confidence: 78%

Spinal Processing of Noxious and Innocuous Cold Information: Differential Modulation by the Periaqueductal Gray

Leith¹,

Koutsikou²,

Lumb³

et al. 2010

J. Neurosci.

View full text Add to dashboard Cite

In addition to cold being an important behavioral drive, altered cold sensation frequently accompanies pathological pain states. However, in contrast to peripheral mechanisms, central processing of cold sensory input has received relatively little attention. The present study characterized spinal responses to noxious and innocuous intensities of cold stimulation in vivo and established the extent to which they are modulated by descending control originating from the periaqueductal gray (PAG), a major determinant of acute and chronic pain. In lightly anesthetized rats, hindpaw cooling with ethyl chloride, but not acetone, was sufficiently noxious to evoke withdrawal reflexes, which were powerfully inhibited by ventrolateral (VL)-PAG stimulation. In a second series of experiments, subsets of spinal dorsal horn neurons were found to respond to innocuous and/or noxious cold. Descending control from the VL-PAG distinguished between activity in nociceptive versus non-nociceptive spinal circuits in that innocuous cold information transmitted by non-nociceptive class 1 and wide-dynamic-range class 2 neurons remained unaltered. In contrast, noxious cold information transmitted by class 2 neurons and all cold-evoked activity in nociceptive-specific class 3 neurons was significantly depressed. We therefore demonstrate that spinal responses to cold can be powerfully modulated by descending control systems originating in the PAG, and that this control selectively modulates transmission of noxious versus innocuous information. This has important implications for central processing of cold somatosensation and, given that chronic pain states are dependent on dynamic alterations in descending control, will help elucidate mechanisms underlying aberrant cold sensations that accompany pathological pain states.

show abstract

Section: Neural Mechanisms Of Cold Somatosensationmentioning

confidence: 78%

Spinal Processing of Noxious and Innocuous Cold Information: Differential Modulation by the Periaqueductal Gray

Leith¹,

Koutsikou²,

Lumb³

et al. 2010

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…5 In the spinal cord, recent studies using more selective agonists and antagonists have implicated primarily A1 receptor in antinociception and A2 receptor in muscle relaxation. 17,18 For both receptor subtypes, dorsal spinal cord levels exceed ventral spinal cord level, and adenosine A1 receptors are selectively concentrated in the substantia gelatinosa. [19][20][21][22] In our study, antihyperalgesic and analgesic effect of adenosine upon visceral pain was mainly mediated via A1 receptor.…”

Section: Discussionmentioning

confidence: 99%

Adenosine Receptor Agonists Modulate Visceral Hyperalgesia in the Rat

Sohn¹,

Park²,

Gebhart³

2008

Gut Liver

View full text Add to dashboard Cite

Background/Aims: Adenosine is an endogenous modulator of nociception. Its role in visceral nociception, particularly in visceral hyperalgesia, has not been studied. The aim of this study was to determine the effects of adenosine receptor agonists in a model of visceral hyperalgesia. Methods: The visceromotor response (VMR) in rats to colorectal distension (CRD; 80 mmHg, 20 seconds) was quantified by electromyographic recordings from the abdominal musculature. Three hours after the intracolonic administration of zymosan (25 mg/mL, 1 mL), VMRs to CRD were measured before and after either subcutaneous or intrathecal administration of an adenosine receptor agonist. Results: Subcutaneous injection of 5'-N-ethylcarboxyamidoadenosine (NECA; an A1 and A2 receptor agonist), R(-)-N6-(2-phenylisopropyl)-adenosine (R-PIA; a selective A1 receptor agonist), or CGS-21680 hydrochloride (a selective A2a receptor agonist) dose-dependently (10-100 mg/kg) attenuated the VMR to CRD, although hindlimb weakness occurred at the higher doses tested. Intrathecal administration of NECA or R-PIA dose-dependently (0.1-1.0μg/kg) decreased the VMR, whereas CGS-21680 hydrochloride was ineffective over the same concentration range. Higher intrathecal doses of the A1/A2 receptor agonist NECA produced motor weakness. Conclusions: Adenosine receptor agonists are antihyperalgesic, but also produce motor weakness at high doses. However, activation of the spinal A1 receptor significantly attenuates the VMR to CRD without producing motor weakness. (Gut and Liver 2008;2:39-46)

show abstract

“…8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist (10 mg 10 ml ; TOCRIS), were dissolved in dimethyl sulfoxide and diluted with phosphate-buffered saline. The doses of all agonists except Cl-adenosine were decided according to previous papers 10,13 that described intrathecal application. Antagonists were used at relatively high concentrations compared with agonists to achieve adequate blockade of the receptors.…”

Section: Drugsmentioning

confidence: 99%

“…8 Several previous studies have shown that intrathecal adenosine receptor agonists inhibit pain behavior after peripheral nerve injuries such as L5-L6 spinal nerve ligation, 9 sciatic nerve ligation, 10 intrathecal strychnine injection, 11 intrathecal administration of excitatory amino acids or substance P 12 and photochemical SCI through laser irradiation. 13 Until now, there has been no reported evidence of anti-hyperalgesic action of adenosine receptor agonists after mechanical spinal cord compression injury. The purpose of this study was to examine the effect of adenosine on hyperalgesia after a spinal cord compression injury.…”

Section: Introductionmentioning

confidence: 99%

Adenosine A1 receptor agonists reduce hyperalgesia after spinal cord injury in rats

et al. 2010

View full text Add to dashboard Cite

Study design: An in vivo study using a spinal cord compression model in rats. Objectives: To evaluate the effect of adenosine on thermal hyperalgesia after spinal cord injury (SCI). Summary of background data: After SCI, some patients suffer dysesthesia that is unresponsive to conventional treatments. We previously established a rat thoracic spinal cord mild-compression model by which we were able to induce thermal hyperalgesia in the hind limbs. Methods: The thoracic spinal cord was compressed gently using a 20-g weight for 20 min. The withdrawal latency in response to thermal stimulation was monitored bilaterally in the hind limbs using Hargreaves' Plantar test apparatus. Results: SCI-induced thermal hyperalgesia was mimicked by the intrathecal application of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist. Hyperalgesia induced by SCI was significantly inhibited by the intrathecal application of 10-30 nmol chloro-adenosine (Cl-adenosine), a nonselective adenosine receptor agonist. The effect of Cl-adenosine (10 nmol) on hyperalgesia after SCI was blocked by the simultaneous application of DPCPX. Intrathecal application of R(À)N6-(2phenylisopropyl) adenosine (R-PIA; 10 nmol), a selective A1 receptor agonist, also inhibited SCI-induced hyperalgesia. In contrast, intrathecal application of CGS21680, a selective adenosine A2a receptor agonist, did not inhibit SCI-induced hyperalgesia. Conclusions: These results suggest that adenosine inhibits hyperalgesia through the stimulation of A1 receptors. Adenosine or adenosine A1 receptor agonists should be considered as candidates for new therapeutic methods for treating post-SCI dysesthesia.

show abstract

Intrathecal administration of the adenosine A1 receptor agonist R-phenylisopropyl adenosine reduces presumed pain behaviour in a rat model of central pain

Cited by 43 publications

References 13 publications

Spinal Processing of Noxious and Innocuous Cold Information: Differential Modulation by the Periaqueductal Gray

Spinal Processing of Noxious and Innocuous Cold Information: Differential Modulation by the Periaqueductal Gray

Adenosine Receptor Agonists Modulate Visceral Hyperalgesia in the Rat

Adenosine A1 receptor agonists reduce hyperalgesia after spinal cord injury in rats

Contact Info

Product

Resources

About